全文获取类型
收费全文 | 6684篇 |
免费 | 379篇 |
国内免费 | 20篇 |
专业分类
7083篇 |
出版年
2024年 | 11篇 |
2023年 | 94篇 |
2022年 | 247篇 |
2021年 | 354篇 |
2020年 | 330篇 |
2019年 | 477篇 |
2018年 | 367篇 |
2017年 | 258篇 |
2016年 | 345篇 |
2015年 | 370篇 |
2014年 | 455篇 |
2013年 | 580篇 |
2012年 | 538篇 |
2011年 | 538篇 |
2010年 | 284篇 |
2009年 | 245篇 |
2008年 | 267篇 |
2007年 | 273篇 |
2006年 | 238篇 |
2005年 | 196篇 |
2004年 | 146篇 |
2003年 | 106篇 |
2002年 | 97篇 |
2001年 | 16篇 |
2000年 | 14篇 |
1999年 | 19篇 |
1998年 | 20篇 |
1997年 | 16篇 |
1996年 | 14篇 |
1995年 | 6篇 |
1994年 | 7篇 |
1993年 | 12篇 |
1992年 | 6篇 |
1991年 | 14篇 |
1990年 | 5篇 |
1989年 | 10篇 |
1988年 | 4篇 |
1987年 | 12篇 |
1986年 | 12篇 |
1985年 | 13篇 |
1984年 | 12篇 |
1983年 | 8篇 |
1982年 | 6篇 |
1981年 | 5篇 |
1980年 | 6篇 |
1976年 | 3篇 |
1974年 | 7篇 |
1973年 | 3篇 |
1963年 | 2篇 |
1962年 | 2篇 |
排序方式: 共有7083条查询结果,搜索用时 15 毫秒
961.
Ronak Patel Mohammad Anwar Hossain Nadezhda German Abraham Jacob Al-Ahmad 《Mycotoxin Research》2018,34(4):257-268
Cerebral fungal infections represent an important public health concern, where a key element of pathophysiology is the ability of the fungi to cross the blood-brain barrier (BBB). Yet the mechanism used by micro-organisms to cross such a barrier and invade the brain parenchyma remains unclear. This study investigated the effects of gliotoxin (GTX), a mycotoxin secreted by Aspergillus fumigatus, on the BBB using brain microvascular endothelial cells (BMECs) derived from induced pluripotent stem cells (iPSCs). We observed that both acute (2 h) and prolonged (24 h) exposure to GTX at the level of 1 μM or higher compromised BMECs monolayer integrity. Notably, acute exposure was sufficient to disrupt the barrier function in iPSC-derived BMECs, resulting in decreased transendothelial electrical resistance (TEER) and increased fluorescein permeability. Further, our data suggest that such disruption occurred without affecting tight junction complexes, via alteration of cell-matrix interactions, alterations in F-actin distribution, through a protein kinase C-independent signaling. In addition to its effect on the barrier function, we have observed a low permeability of GTX across the BBB. This fact can be partially explained by possible interactions of GTX with membrane proteins. Taken together, this study suggests that GTX may contribute in cerebral invasion processes of Aspergillus fumigatus by altering the blood-brain barrier integrity without disrupting tight junction complexes. 相似文献
962.
Mohammad Asadi 《Mycotoxin Research》2018,34(1):15-20
A rapid, simple, and green vortex-assisted emulsification microextraction method based on solidification of floating organic drop was developed for the extraction and determination of ochratoxin A (OTA) with high-performance liquid chromatography. Some factors influencing the extraction efficiency of OTA such as the type and volume of extraction solvent, sample pH, salt concentration, vortex time, and sample volume were optimized. Under optimized conditions, the calibration curve exhibited linearity in the range of 50.0–500 ng L?1 with a coefficient of determination higher than 0.999. The limit of detection was 15.0 ng L?1. The inter- and intra-assays relative standard deviations were in a range of 4.7–8.7%. The accuracy of the developed method was investigated through recovery experiments, and it was successfully used for the quantification of OTA in 40 samples of fruit juice. 相似文献
963.
Johannes Hachmann Mohammad Atif Faiz Afzal Mojtaba Haghighatlari Yudhajit Pal 《Molecular simulation》2018,44(11):921-929
AbstractThe use of modern data science has recently emerged as a promising new path to tackling the complex challenges involved in the creation of next-generation chemistry and materials. However, despite the appeal of this potentially transformative development, the chemistry community has yet to incorporate it as a central tool in every-day work. Our research program is designed to enable and advance this emerging research approach. It is centred around the creation of a software ecosystem that brings together physics-based modelling, high-throughput in silico screening and data analytics (i.e. the use of machine learning and informatics for the validation, mining and modelling of chemical data). This cyberinfrastructure is devised to offer a comprehensive set of data science techniques and tools as well as a general-purpose scope to make it as versatile and widely applicable as possible. It also emphasises user-friendliness to make it accessible to the community at large. It thus provides the means for the large-scale exploration of chemical space and for a better understanding of the hidden mechanisms that determine the properties of complex chemical systems. Such insights can dramatically accelerate, streamline and ultimately transform the way chemical research is conducted. Aside from serving as a production-level tool, our cyberinfrastructure is also designed to facilitate and assess methodological innovation. Both the software and method development work are driven by concrete molecular design problems, which also allow us to assess the efficacy of the overall cyberinfrastructure. 相似文献
964.
Josephine Herbst Annabel Girke Mohammad Reza Hajirezaei Guy Hanke Bernhard Grimm 《The Plant journal : for cell and molecular biology》2018,94(3):485-496
Chlorophyll is synthesized from activated glutamate in the tetrapyrrole biosynthesis pathway through at least 20 different enzymatic reactions. Among these, the MgProto monomethylester (MgProtoME) cyclase catalyzes the formation of a fifth isocyclic ring to tetrapyrroles to form protochlorophyllide. The enzyme consists of two proteins. The CHL27 protein is proposed to be the catalytic component, while LCAA/YCF54 likely acts as a scaffolding factor. In comparison to other reactions of chlorophyll biosynthesis, this enzymatic step lacks clear elucidation and it is hardly understood, how electrons are delivered for the NADPH‐dependent cyclization reaction. The present study intends to elucidate more precisely the role of LCAA/YCF54. Transgenic Arabidopsis lines with inactivated and overexpressed YCF54 reveal the mutual stability of YCF54 and CHL27. Among the YCF54‐interacting proteins, the plastidal ferredoxin‐NADPH reductase (FNR) was identified. We showed in N. tabacum and A. thaliana that a deficit of FNR1 or YCF54 caused MgProtoME accumulation, the substrate of the cyclase, and destabilization of the cyclase subunits. It is proposed that FNR serves as a potential donor for electrons required in the cyclase reaction and connects chlorophyll synthesis with photosynthetic activity. 相似文献
965.
Shahnaz Ibrahim Saadia Maqbool Maleeha Azam Mohammad Perwaiz Iqbal Raheel Qamar 《Molecular biology reports》2018,45(3):353-360
Three index patients with hyperhomocysteinemia and ocular anomalies were screened for cystathionine beta synthase (CBS) and methylenetetrahydrofolate reductase (MTHFR) polymorphisms. Genotyping of hyperhomocysteinemia associated MTHFR polymorphisms C677T (rs1801133) and A1298C (rs1801131) was done by PCR-restriction fragment length polymorphism. Sanger sequencing was performed for CBS exonic sequences along with consensus splice sites. In the case of MTHFR polymorphisms, all the patients were heterozygous CT for the single nucleotide polymorphism (SNP) C677T and were therefore carriers of the risk allele (T), while the patients were homozygous CC for the risk genotype of the SNP A1298C. CBS sequencing resulted in the identification of two novel mutations, a missense change (c.467T>C; p.Leu156Pro) in exon 7 and an in-frame deletion (c.808_810del; p.Glu270del) in exon 10. In addition, a recurrent missense mutation (c.770C>T; p.Thr257Met) in exon 10 of the gene was also identified. The mutations were present homozygously in the patients and were inherited from the carrier parents. This is the first report from Pakistan where novel as well as recurrent CBS mutations causing hyperhomocysteinemia and lens dislocation in three patients from different families are being reported with the predicted effect of the risk allele of the MTHFR SNP in causing hyperhomocysteinemia. 相似文献
966.
Nobakht-Haghighi Navid Rahimifard Mahban Baeeri Maryam Rezvanfar Mohammad Amin Moini Nodeh Shermineh Haghi-Aminjan Hamed Hamurtekin Emre Abdollahi Mohammad 《Molecular and cellular biochemistry》2018,449(1-2):267-276
Molecular and Cellular Biochemistry - Oxidative stress has been involved in the aging process and the pathogenesis of type-2 diabetes, which is a serious health problem worldwide. This study... 相似文献
967.
Discovery of potent polyphosphate kinase 1 (PPK1) inhibitors using structure‐based exploration of PPK1Pharmacophoric space coupled with docking analyses 下载免费PDF全文
Rasha M. Bashatwah Mohammad A. Khanfar Sanaa K. Bardaweel 《Journal of molecular recognition : JMR》2018,31(10)
Inorganic polyphosphate (polyP) is present in all living forms of life. Studied mainly in prokaryotes, polyP and its associated enzymes are vital in diverse metabolic activities, in some structural functions, and most importantly in stress responses. Bacterial species, including many pathogens, encode a homolog of a major polyP synthesis enzyme, Poly Phosphate Kinase (PPK) with 2 different genes coding for PPK1 and PPK2. Genetic deletion of the ppk1 gene leads to reduced polyP levels and the consequent loss of virulence and stress adaptation responses. This far, no PPK1 homolog has been identified in higher‐order eukaryotes, and, therefore, PPK1 represents a novel target for chemotherapy. The aim of the current study is to investigate PPK1 from Escherichia coli with comprehensive understanding of the enzyme's structure and binding sites, which were used to design pharmacophores and screen a library of compounds for potential discovery of selective PPK1 inhibitors. Verification of the resultant inhibitors activities was conducted using a combination of mutagenic and chemical biological approaches. The metabolic phenotypic maps of the wild type E. coli (WT) and ppk1 knockout mutant were generated and compared with the metabolic map of the chemically inhibited WT. In addition, biofilm formation ability was measured in WT, ppk1 knockout mutant, and the chemically inhibited WT. The results demonstrated that chemical inhibition of PPK1, with the designed inhibitors, was equivalent to gene deletion in altering specific metabolic pathways, changing the metabolic fingerprint, and suppressing the ability of E. coli to form a biofilm. 相似文献
968.
969.
970.